Certain metals (Al, Cd, and Fe) are known to cause orthopedic pathologies in humans and animals. Little is known about the mechanism of action of metals on either the formation of bone or on the physical chemical properties of the mineral phase. This study will test the hypothesis that these metals directly affect the formation and properties of hydroxyapatite (bone mineral), and thereby, are a causative factor of this metal-related defective bone formation. The effect on hydroxyapatite formation, of other metals. (Cr, V, Ti, Ni, Co), used in orthopedic joint prostheses, and zinc, which accumulates at the bone mineralization front, will also be investigated. The work will be divided into four areas of study. First, the effect of various metal ions on the formation and growth of hydroxyapatite (HA) will be determined in three biologically relevant test systems: (a) the transformation of amorphous calcium phosphate (ACP) to HA; (b) the direct formation of HA at low supersaturation; and (c) the growth of HA on HA seed crystals. Second, the formation of HA by diffusion of Ca and PO4 ions into collagen gels will be studied in the presence of various metal ions, the collagen gel serving as a medium to simulate the function of the calcifying matrices in vivo. Third, the structure and crystallization kinetics of amorphous metal phosphates and metal containing amorphous calcium phosphates (ACP's) will be studied by x-ray diffraction (XRD) and x-ray radial distribution function analysis (RDF) to elucidate; (a) the chemistry and atomic structure of these metal phosphates, and (b) possible mechanisms by which these metals may interfere with mineralization in metal-related bone diseases. Fourth, rats will be injected with the metal ions used in the above studies. The long bones will be subjected to XRD and IR examination, as well as analysis for Ca, PO4, and metal ions, ash weight determination, and density fractionation. The effect of the metal ions on these parameters will be investigated by a comparison to control rat bone, which will show the relation between changes in bone mineral properties and the bone diseases induced by these metal ions.